Malaria-Infected Mice Live until at Least Day 30 after a New Monomeric Trioxane Combined with Mefloquine Are Administered Together in a Single Low Oral Dose

详细信息    查看全文

• 作者：Lauren E. Woodard ; Wonsuk Chang ; Xiaochun Chen ; Jun O. Liu ; Theresa A. Shapiro ; Gary H. Posner
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：December 10, 2009
• 年：2009
• 卷：52
• 期：23
• 页码：7458-7462
• 全文大小：768K
• 年卷期：v.52,no.23(December 10, 2009)
• ISSN：1520-4804

文摘

In only five simple steps and 48% overall yield from the natural trioxane artemisinin, the thermally and hydrolytically stable trioxane fluoroanilide 4b has been prepared. Upon one oral dose of only 6.8 mg/kg of monomeric trioxane 4b combined with 20 mg/kg of mefloquine hydrochloride, all of the malaria-infected mice lived until at least day 30 post infection. Of the five mice in this surviving group, four (80%) were completely cured (no parasites in their blood) and one mouse had 4% blood parasitemia. Importantly, the efficacy of this ACT chemotherapy using monomeric trioxane 4b plus mefloquine hydrochloride is considerably better than the efficacy under the same conditions using the popular trioxane drug artemether plus mefloquine hydrochloride.